Obesity and Type 2 Diabetesin children and adolescents

Eva Tsalikian M.D.

Stead family Department of Pediatrics

Pediatric Endocrinology and Diabetes

April 16, 2014

Obesity and Type 2 Diabetesin children and adolescents: outline

• Epidemiology and definitions• Pathophysiology of Type 2 diabetes• Obesity leading to metabolic syndrome and Type 2 diabetes• Treatment of Type 2 Diabetes in children and

adolescents• Case presentations

Rates of Overweight and Obese Children

2005 2007

The problem in children and adolescents

•Approximately 17% (or 12.5 million) of children and adolescents aged 2—19 years are obese.

• In 2011-2012, 8.4% of 2- to 5-year-olds were obese compared with 17.7% of 6- to 11-year-olds and 20.5% of 12- to 19-year-olds.

• The prevalence of obesity among children aged 2 to 5 years decreased significantly from 13.9% in 2003-2004 to 8.4% in 2011-2012.

Identification

Children (Ages 6 to 11)

Prevalence (%)

Adolescents (Ages 12 to 19)Prevalence (%)

Race Overweight Obesity Overweight Obesity

Black (Non-Hispanic) 35.9 19.5 40.4 23.6

Mexican American 39.3 23.7 43.8 23.4

White (Non-Hispanic) 26.2 11.8 26.5 12.7

Source: CDC, National Center for Health Statistics, National Health and Nutrition Examination Survey. Ogden et. al. JAMA. 2002;288:1728-1732.

Why is this a problem?• Overweight children become overweight adults• Risk for diabetes, cardiovascular disease and many

other chronic diseasesBefore becoming adults:• Psychological and self image problems• Medical problems: hypertension, dyslipidemia,

diabetes

DIABETES :IN CHILDREN AND ADOLESCENTS

HISTORICALLY

• Type 1 Diabetes

• Prevalence 1 in 500

• TYPE 1 DIABETES 95-98%

• OTHER TYPES OF DIABETES 2-5%

TYPE 2 DIABETES

DEFINITION• Syndrome associated with obesity, hypertension and

cardiovascular disease

• Characterized by both peripheral resistance to insulin action and insulin secretory defects

• Historically rare in children and adolescents, incidence has been increasing recently

DIAGNOSIS OF DIABETES

World Health Organization and

American Diabetes Association

• Fasting blood glucose 126 mg/dL

• Post prandial glucose >200mg/dL

• Oral glucose Tolerance test not always necessary

• Elevated HgA1c

Type 2 Diabetes Risk Factors and Testing Criteria

Who to screen?•Overweight (BMI >85th percentile for age and gender; weight for height >85th percentile; or weight >120 percent of ideal for height

•PLUS Any two of the following risk factors

--family history of type 2 diabetes in first- or second-degree relative

--race/ethnicity – American Indian, African American, Hispanic/Latino, Asian American, or Pacific Islander

--signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, polycystic ovarian syndrome, or small-for-gestational-age birth weight)

-- maternal history of diabetes or GDM during the child’s gestation

When and how to screen

• Age to begin testing – 10 years old or at onset of puberty if puberty occurs earlier

• Frequency of testing – every 3 years• Tests to use – fasting plasma glucose, A1C, 2-h

oral glucose tolerance test• Clinical judgment should be used to perform

testing in children and adolescents who do not meet the above criteria.

Type 2 diabetes in children :World wide phenomenon

TYPE 2 DIABETES

PATHOPHYSIOLOGY

• Failure of insulin secretion to compensate for insulin resistance associated with obesity, in most cases

• Evidence of both genetically limited beta-cell reserve and heritable insulin resistanceIn Adolescents• Pubertal insulin resistance compounded by obesity

results in type 2 diabetes• Polycystic ovarian syndrome (PCOS) in adolescent

females

Case presentation

• 11 year old boy was referred because father, who was recently diagnosed with Type 2 Diabetes, noted similar symptoms in son i.e. Polyuria, polydipsia, nocturia. Twelve lbs weight loss was noted.

• Child is overweight, no other abnormal findings.• Fasting blood sugar 124 mg/dl. OGTT did not meet

criteria for diagnosis of diabetes.

• Hg A1c 6% (4.2-6%)

Physical characteristics in children and adolescents with diabetes

BMI in New onset Type 2 Diabetes

Why Are They Obese?

• Endocrine disorders– Hypothyroidism– Glucocorticoid excess (iatrogenic or endogenous)– Growth hormone deficiency– All cause linear growth failure associated with short stature

• Genetic syndromes– Prader-Willi– Bardet-Biedl (mental retardation, hypogonadism, polydactyly,

retinitis pigmentosa)– Albright’s hereditary osteodystrophy (short stature, short fourth

metacarpal, mental retardation, hypocalcemia)• Exogenous

– usually tall above the 75th - 95th %ile– usually familial

Exogenous Obesity

• Nature versus Nurture

– Appetite

– Efficient metabolism

– Decreased exercise

– Altered body image

What Can We Do About Childhood Obesity?

• Identify medical risk factors

– Blood pressure

– Cholesterol levels

– Sleep apnea

– Diabetes

• Identify and treat medical causes.

– Hypothyroidism, Cushing’s syndrome

– Prader-Willi Syndrome

Prevention

• Lifestyle changes: Decreased caloric intake and increased physical activity extremely challenging

• Pharmacologic intervention to reduce weight is not yet deemed appropriate for children

Case Presentation

• Obese 11y old w boy, no symptoms • Distant family history of type 2 Diabetes• Fasting and random blood glucose within

normal limits• HgA1c 5.9% (4.2-6%)• Serum insulin 687uIU/ml (5-20uIU/ml)

Relationship between Insulin resistance, metabolic syndrome and Diabetes

Insulin resistance

HyperinsulinemiaInadequateInsulin secretion

Metabolic syndrome

Type 2 Diabetes

When should we intervene?

Size of populationSize of population

Preventionof weight gain

Overweightand obesity

Insulin resistanceMetabolicsyndrome

IGTDiabetes HypertensionHyperlipidemia

                                                          

Effects of metformin on fasting glucose and insulin levels in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes mellitus. Freemark, M et al JCEM, 88(1):3

TYPICAL CASE PRESENTATION

• 15 yr old w boy seen for routine sports physical: Asymptomatic

UA: +glucose and ketones

• HISTORY of nocturia x1 for the last 2-6mo and 11 lbs wt loss

• FAMILY HISTORY positive for Type 2 Diabetes in maternal grandfather

• PE : HT 75th % WT >>95th % BP130/68

TYPICAL CASE PRESENTATION (continued)

• Fasting blood sugars locally on three different mornings : 208, 140, 153 mg/dl

• HgA1c 6.6% (4.5-6%)• Fasting glucose, Insulin, c-peptide • No autoimmune markers

• Diagnosis : Type 2 Diabetes• Therapeutic Plan: Diet and Exercise Blood glucose monitoring

Treatment of children and adolescents with type 2 diabetes

• Goals of treatment are weight loss, normoglycemia and normal HgA1c.

• Young age at onset of type 2 diabetes means longer duration and thus more microvascular and macrovascular complications: Grave public health implications.

• 33% will have ketosis and 10% ketoacidosis: require insulin

Therapeutic options in children and adolescents with Type 2 diabetes

• Weight control through diet and exercise

• Oral hypoglycemic agents

• Insulin

TYPICAL CASE PRESENTATION (continued)

• 3 month follow up: Wt loss, HgA1c

• Further Follow up : Wt gain, HgA1c

• Hypoglycemic agents

TODAY Study

• 15 clinical centers funded by NIDDK• 699 adolescents with Type 2 diabetes

Participants randomized 1:1:1 to(i) metformin alone(ii) metformin plus rosiglitazone(iii) metformin plus an intensive lifestyle

intervention called the TODAY Lifestyle Program (TLP)

TODAY Study

Effects of Metformin, Metformin Plus Rosiglitazone, and Metformin Plus Lifestyle on Insulin Sensitivity

Prevalence of Hypertension

In Summary: Testing children and adolescents

for type 2 diabetes• Criteria Overweight (BMI >85% for age and sex)• Risk factors (any two) Family history of type 2 diabetes, Race/ ethnicity, Signs of insulin resistance: Acanthosis

Nigricans, Hypertension, dyslipidemia, PCOS• Age of initiation: 10 years of age • Frequency: every 2-3 years• Test: FPG preferred

In Summary: Approach to Treatment

• Prevention of type 2 diabetes needs to start at young ages

• Diet and exercise interventions should be started early in high risk individuals

• Delaying the onset of type 2 diabetes may also be a significant benefit

• Therapy might need to be individualized (e.g. boys better with Lifestyle +metformin, girls metformin +TZD, NHB vs Hispanics)

• Polypharmacy may be required

In Summary: Treatment of Type 2 diabetes in children

Nonpharmacologic Rx(weight control, activity)

MonotherapyMetformin

Combination therapyMetformin, Rosiglitazone

•Severe hyperglycemia•very symptomatic •ketosis •autoimmune markers

Insulin + Metformin

Thank you!!!